{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T19:21:22Z","timestamp":1789154482216,"version":"build-2803163510"},"reference-count":33,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,3,3]],"date-time":"2022-03-03T00:00:00Z","timestamp":1646265600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["436 RUS 113\/11"],"award-info":[{"award-number":["436 RUS 113\/11"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002261","name":"Russian Foundation for Basic Research","doi-asserted-by":"publisher","award":["98-04-04106"],"award-info":[{"award-number":["98-04-04106"]}],"id":[{"id":"10.13039\/501100002261","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Nitric oxide (NO) is a powerful vasodilator in different vascular beds and NO-donors are widely used in clinical practice. Early data suggested that NO and NO-donors activate vascular smooth muscle high-conductance, calcium-activated potassium channels (BK channels). There exist two hypotheses explaining the effect of NO and NO-donors on BK channels\u2014one stating that protein kinase G (PKG) mediates the effect of NO, and the other one stating that NO acts directly on the channel. Thus, the degree of contribution of PKG to the NO-induced activation of the BK channel is still not completely clear. This study tested the hypothesis that the sodium nitroprusside (SNP)-induced activation of vascular smooth muscle BK channels is fully mediated by PKG. This hypothesis was investigated using the patch-clamp technique and freshly isolated smooth muscle cells from rat tail artery. In whole-cell experiments, SNP considerably increased the outward current compared with the addition of the bath solution. SNP did not alter the current in the presence of iberiotoxin, the specific blocker of BK channels, during co-application with hydroxocobalamin, an NO-scavenger, and in the presence of Rp-8-Br-PET-cGMPS, the specific PKG-inhibitor. In inside-out patches, the activity of BK channels was increased by SNP, SNAP, and DEA-NO. However, these effects did not differ from the effect of the application of drug-free bath solution. Furthermore, a similar increase in single BK channel activity was induced by Rp-8-Br-PET-cGMPS, Rp-8-Br-PET-cGMPS together with SNP, hydroxocobalamin, and hydroxocobalamin together with SNP or DEA-NO. Finally, the activity of excised BK channels did not change in the absence of any application but was considerably increased by PKG compared with the addition of drug-free bath solution. These results suggest that NO released from NO-donors stimulates the BK current only through activation of PKG.<\/jats:p>","DOI":"10.3390\/ijms23052798","type":"journal-article","created":{"date-parts":[[2022,3,3]],"date-time":"2022-03-03T09:24:53Z","timestamp":1646299493000},"page":"2798","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Sodium Nitroprusside-Induced Activation of Vascular Smooth Muscle BK Channels Is Mediated by PKG Rather Than by a Direct Interaction with NO"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2759-7981","authenticated-orcid":false,"given":"Hristo","family":"Gagov","sequence":"first","affiliation":[{"name":"Department of Animal and Human Physiology, Faculty of Biology, St. Kliment Ohridski University of Sofia, 1164 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7757-318X","authenticated-orcid":false,"given":"Irina","family":"Gribkova","sequence":"additional","affiliation":[{"name":"Scientific and Clinical Department, State Budgetary Institution \u00abResearch Institute for Healthcare Organization and Medical Management of Moscow Healthcare Department\u00bb, 115088 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Serebryakov","sequence":"additional","affiliation":[{"name":"Institute of Experimental Cardiology, Cardiology Research Center, 121552 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1777-1461","authenticated-orcid":false,"given":"Rudolf","family":"Schubert","sequence":"additional","affiliation":[{"name":"Physiology, Institute of Theoretical Medicine, Faculty of Medicine, University of Augsburg, 86159 Augsburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9360","DOI":"10.1073\/pnas.85.23.9360","article-title":"Guanosine 5\u2032-monophosphate modulates gating of high-conductance Ca2+-activated K+ channels in vascular smooth muscle cells","volume":"85","author":"Williams","year":"1988","journal-title":"Proc. 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